Wound care formulations with clinically effective ingredient content

ABSTRACT

The disclosed wound-healing formulation adds ingredients from the group consisting of camphor, menthol and eucalyptus to known silver sulfadiazine-based formulations, or to known silver sulfadiazine-and-urogastrone-based formulations, preferably for the topical treatment of skin wounds such as cuts, burns, surgical wounds, etc. Preferred embodiments are in cream form. The disclosed formulation shows unexpected and startling improvement in wound healing rates over expected healing rates using the known silver sulfadiazine-based or silver sulfadiazine-and-urogastrone-based formulations alone.

RELATED APPLICATIONS

This application is a continuation of co-pending U.S. nonprovisionalpatent application Ser. No. 16/458,796 filed Jul. 1, 2019 (shortly to beU.S. Pat. No. 10,695,356), which itself is a continuation of U.S.nonprovisional patent application Ser. No. 15/905,632 filed Feb. 26,2018 (now U.S. Pat. No. 10,335,421). The entire disclosures of Ser. Nos.16/458,796 and 15/905,632 are incorporated herein by reference.

FIELD OF THE DISCLOSURE

This disclosure is directed generally to a wound care formulation,preferably in cream form, that is both stable and bioeffective. Broadly,and without limiting the scope of this disclosure, one embodiment of theformulation is a urogastrone camphor eucalyptus menthol creamformulation for topical administration in a silver sulfadiazine basecontaining propylene glycol. Additional embodiments are also disclosed.

BACKGROUND OF THE DISCLOSED TECHNOLOGY

Antimicrobial creams are known to promote skin and soft tissue woundhealing via topical administration. Such antimicrobial creams typicallydemonstrate improvement in wound healing as well as more rapid closureof wounds. In this way, such topical antimicrobial creams decreaseinfection and inflammation commonly associated with wounds, scars, andburns. More specifically, topical antimicrobial creams will generallyrelieve redness and inflammation, and will increase the speed andquality of wound healing. There is a correlation between the therapeuticeffects of these creams and their healing potentials.

Topical antimicrobial products are commercially available in variousmedia, such as lotions, creams, ointments, and gels. A key activeingredient in one class of commercially-available antimicrobial creamsis silver sulfadiazine. Hebermin and Silvadene® are brand names forknown topical antimicrobial creams containing silver sulfadiazine. Eachdemonstrate serviceable healing performance in the treatment of skinwounds.

Hebermin is stated as having the following ingredients: Silversulfadiazine 1%, urogastrone 0.001%, stearyl alcohol, petrolatum,polyoxyl 40 stearate, propylene glycol, isopropyl myristate, andsorbitan monooleate with methylparaben 0.3%.

Silvadene® is stated as having similar ingredients to Hebermin withoutthe urogastrone.

It is always advantageous to reduce the healing time for skin wounds.The quicker a wound heals, the less downtime the patient sustains withlimited mobility and discomfort. Quicker healing also reduces the riskof infection. It would therefore be highly advantageous if the healingperformance of existing silver sulfadiazine-based topical creams such asHebermin and Silvadene® could be accelerated to provide even betterhealing performance in a shorter period of time.

SUMMARY AND TECHNICAL ADVANTAGES

These and other drawbacks in the prior art are addressed by thedisclosed embodiments of an inventive formulation that, in currentlypreferred embodiments, is administered to wounds in topical cream form.Although currently preferred embodiments of the formulation are in creamform, it will be nonetheless appreciated that the scope of thisdisclosure is not limited in this regard. Other embodiments of thedisclosed formulation may be, for example, in solution form. The creamis currently branded “Compone CS”. Disclosed embodiments of theinventive formulation add ingredients from the group consisting ofcamphor, menthol and eucalyptus to known silver sulfadiazine-basedformulations such as Hebermin or Silvadene®. In embodiments wherecamphor is added, camphor is preferably added in quantities in a rangebetween about 0.5% to about 20%, and more preferably in a range betweenabout 10% to about 20%. In embodiments where menthol is added, mentholis preferably added in quantities in a range between about 1% to about30%, and more preferably in a range between about 9% to about 30%. Inembodiments in which eucalyptus is added, eucalyptus is preferably addedin quantities in a range between about 2% to about 10%, and morepreferably in a range between about 2% to about 5%. It will benonetheless appreciated that the scope of the disclosed wound-healingformulation is not limited to the foregoing camphor, menthol and/oreucalyptus ingredient percentages.

Currently preferred embodiments of the disclosed wound-healingformulation are in cream form, are stable, and carry a biologicallyeffective amount of silver sulfadiazine, urogastrone, and ingredientsfrom the group consisting of camphor, menthol and eucalyptus. Such creamembodiments preferably also include balanced amounts of hydrophilic andlipophilic surfactants with other preservatives. The hydrophilic basecreates and maintains the needed therapeutic concentration of the activeingredients in the precise area of the wound to be treated. Examples andactual cases show cream embodiments of the disclosed wound-healingformulation to be highly effective in stimulating cellular proliferationin wounds, while reducing bacterial growth. In particular, withoutlimitation, the disclosed wound-healing formulation has shown itself tobe highly effective against gram positive and gram negative bacteria,dermatophytes, and candida types of fungus.

One exemplary embodiment of the disclosed wound-healing formulation isaccording to the following formulation:

Silver sulfadiazine 1%

Urogastrone 0.001% Water

Stearyl alcohol

Petrolatum

Polyoxyl 40 stearateIsopropyl myristateSorbitan monooleate with methylparaben 0.3%Propylene glycol

Camphor 5% Menthol 10% Eucalyptus 4%

It will be appreciated, however, that the foregoing embodiment isexemplary only, and that the scope of the disclosed wound-healingformulation is not limited to the foregoing embodiment.

Topically applied to wounds, embodiments of the disclosed wound-healingformulation substantially accelerate the healing rate over what might beexpected in treatment with, for example, silver sulfadiazine/urogastrone(e.g. Hebermin) or silver sulfadiazine (e.g. Silvadene®) by itself. Inmore detail, the addition of ingredients from the group consisting ofcamphor, menthol and eucalyptus to known silver sulfadiazine-basedformulations such as Hebermin or Silvadene® shows a remarkable,unexpected and unprecedented improvement in the rate of healing in thetreatment of wounds. Embodiments of the disclosed wound-healingformulation have proven to be highly effective in the treatment ofwounds including, without limitation, arterial wounds, venous wounds,post-operative and other surgical wounds, burns, dehisced wounds andulcerations. Exemplary applications further include treating woundssecondary to injury, trauma burns, diabetes, ulcer treatment, radiation,acne scars, stasis dermatitis, and peripheral vascular disease (“PVD”).Embodiments of the disclosed formulation have proven to substantiallydecrease wound healing time as compared to corresponding healing timefor wounds treated with known silver sulfadiazine-based formulationsalone (i.e. without the additional camphor, menthol and/or eucalyptus).Embodiments of the disclosed wound-healing formulation have furtherproven to completely resolve some wounds treated where prior applicationof known silver sulfadiazine-based formulations, or treatment with knownformulations consisting mainly of camphor, menthol and/or eucalyptus bythemselves, proved not to be efficacious.

Topical administration of camphor, menthol and/or eucalyptus bythemselves are well known for certain limited therapeutic effects.Camphor, menthol and eucalyptus are readily absorbed through the skin.The known therapeutic effects include soothing. Topically-appliedcamphor is known to selectively stimulate nerve endings sensitive tocold, producing a warm sensation when vigorously applied, or a coolsensation when applied gently. This known nerve stimulation effect alsoinduces a slight local anesthesia, promotes blood flow to the contactregion (vasodilation), and has an antimicrobial secondary effect. Thesensation of heat or cold that camphor produces on the skin is known tobe caused by activating an ion channel, which may in turn account forthe antimicrobial secondary effect.

Topical administration of menthol by itself is also well known forcertain therapeutic effects. For example, menthol is widely used indentistry and oral care as a topical analgesic and antibacterial agent.Menthol's topical analgesic properties are also known in the relief ofsprains, minor aches and pains. Well-known products such as “Bengay” or“Icy Hot” are known to contain menthol by itself, or camphorwith/menthol. Similar to camphor, topically-applied menthol also has asoothing effect arising from a cooling sensation felt in the areas onwhich it is administered. As such, menthol-based creams are known forthe treatment of sunburn, for example.

Topical administration of eucalyptus by itself is also well known forrelief of many of the same symptoms addressed by camphor and menthol.For example, topical administration of eucalyptus by itself is known forsoothing, analgesic and antiseptic effects, as well as relief of itching(such as in pruritus). Eucalyptus is also known to lower blood sugar.

While topically-administered camphor, menthol and eucalyptus productsare known to have the foregoing limited therapeutic effects bythemselves, they are generally understood to provide “relief” ratherthan “healing”. Many topical camphor, menthol and eucalyptus productsare “over the counter” products, and are intended to provide relief ofsymptoms while the body engages its own natural healing process. Verylittle, if anything, in the known topical administration of camphor,menthol and eucalyptus products actually reduces healing time. Rather,as noted, the topical administration of camphor, menthol and eucalyptusproducts provides relief from discomfort while the body heals at itsusual rate.

In sharp contrast, examples and actual case studies set forth in the“Detailed Description” section below demonstrate the unexpected andunprecedented improvement in the rate of healing in the treatment ofskin wounds seen from the topical administration of embodiments of thedisclosed wound-healing formulation (in which ingredients from the groupconsisting of camphor, menthol and eucalyptus are added to known silversulfadiazine-based formulations). Conventionally, the addition of suchingredients to known silver sulfadiazine-based formulations might havebeen expected to provide some relief of the patient's symptoms while thehealing rate continued consistent with known healing rates seen in theadministration of such known silver sulfadiazine-based formulations.Nothing (as of yet) cogently explains the unexpected and startlingimprovement in healing rate seen in the examples and case studies setforth below when ingredients from the group consisting of camphor,menthol and eucalyptus are added to the silver sulfadiazine-basedformulations.

The unexpected improvement in wound healing rate seen with the disclosedwound-healing formulation manifests itself in unexpected rates of bothepithelial and epidermal cell regeneration, and in the formation of newgranulation tissue. Corresponding unexpected improvements are seen inthe rate of protein production, collagen collection, and the formationof blood vessels during the healing process. In hindsight, none of theseimproved wound-healing rates or effects would be expected from theaddition of ingredients such as camphor, menthol and/or eucalyptus tosilver sulfadiazine-based formulations. However, further work is neededin this area to understand better, at the molecular or nano level, whyingredients from the group consisting of camphor, menthol and eucalyptusunexpectedly accelerate the rate of healing far beyond what might beexpected if one or more of such ingredients had been added merely toprovide known relief of symptoms.

It is therefore a technical advantage of the disclosed wound-healingformulation to accelerate the rate of healing of skin wounds such ascuts, burns, surgical wounds, etc.

Another technical advantage of the disclosed wound-healing formulationis to heal skin wounds whose healing has been unresponsive to treatmentwith conventional silver sulfadiazine-based formulations.

Another technical advantage of the disclosed wound-healing formulationlies in the delivery system of currently preferred embodiments in creamform. Delivery systems of topical drug products play an important rolein the success and solidity of the product. The cream embodiments of thedisclosed wound-healing formulation allow easy application of theproduct on the skin, and good absorption of the active ingredients intothe wound being treated.

A further technical advantage of the disclosed wound-healing formulationis that embodiments thereof in cream form are stable. Long termstability is important in the commercialization of a cream commodity, inorder to sustain a commercially viable shelf life.

A further technical advantage of the disclosed wound-healing formulationis that wounds healed with the formulation generally have a pleasingcosmetic appearance.

According to a first aspect, therefore, this disclosure describesembodiments of a topical formulation, comprising: (a) silversulfadiazine; and (b) at least one ingredient selected from the groupconsisting of: (1) camphor; (2) menthol; and (3) eucalyptus. In someembodiments, the formulation may further comprise (c) urogastrone. Insome embodiments, the formulation may further comprise at least twoingredients selected from the group consisting of: (1) camphor: (2)menthol; and (3) eucalyptus, which embodiments may further comprise (c)urogastrone. In some embodiments, the formulation may include about 1%silver sulfadiazine. In some embodiments, the formulation may includeabout 0.001% urogastrone. In some embodiments, the formulation mayinclude about 0.5% to about 20% camphor. In some embodiments, theformulation may include about 1% to about 30% menthol. In someembodiments, the formulation may include about 2% to about 10%eucalyptus. In some embodiments, the formulation may include about 0.5%to about 20% camphor and about 1% to about 30% menthol. In someembodiments, the formulation may include about 0.5% to about 20% camphorand about 2% to about 10% eucalyptus. In some embodiments, theformulation may include about 1% to about 30% menthol and about 2% toabout 10% eucalyptus.

According to a second aspect, this disclosure describes embodiments of atopical formulation, comprising: (a) silver sulfadiazine; (b) camphor;(c) menthol; and (d) eucalyptus. In some embodiments, the formulationmay further comprise (e) urogastrone. In some embodiments, theformulation may include about 1% silver sulfadiazine. In someembodiments, the formulation may include about 0.001% urogastrone. Insome embodiments, the formulation may include about 0.5% to about 20%camphor, about 1% to about 30% menthol, and about 2% to about 10%eucalyptus.

According to a third aspect, this disclosure describes embodiments of atopical formulation, comprising: (a) about 1% silver sulfadiazine; (b)about 0.001% urogastrone; and (c) at least one ingredient selected fromthe group consisting of: (1) about 0.5% to about 20% camphor; (2) about1% to about 30% menthol; and (3) about 2% to about 10% eucalyptus. Inother embodiments, the formulation may further comprise at least twoingredients selected from the group consisting of: (1) about 0.5% toabout 20% camphor; (2) about 1% to about 30% menthol; and (3) about 2%to about 10% eucalyptus.

The foregoing has outlined rather broadly some of the features andtechnical advantages of the disclosed wound-healing formulation, inorder that the detailed description that follows may be betterunderstood. Additional features and advantages of the disclosedwound-healing formulation may be described. It should be appreciated bythose skilled in the art that the conception and the specificembodiments disclosed may be readily utilized as a basis for modifyingor designing other formulations for carrying out the same inventivepurposes of the disclosed technology, and that these equivalentformulations do not depart from the spirit and scope of the technologyas described and as set forth in the appended claims.

DETAILED DESCRIPTION

As noted above in the “Summary” section, the disclosed wound-healingformulation, currently branded “Compone CS”, is an effective drug withexcellent anti-microbial, wound healing, bactericidal properties. Intest cases, topical administration of embodiments of the disclosedwound-healing formulation in cream form have demonstrated substantiallyincreased epithelization, substantially increased production ofgranulation, and substantially increased cellular proliferation. Thecream has demonstrated significant reduction in the amount of timerequired to achieve an area of granulation necessary to close wounds.The cream is further useful in wound treatment by extravasation ofcytostatics. As a result, the time for wounds to heal and become closedhas substantially decreased as compared to known silversulfadiazine-based compounds.

The following are examples and actual cases demonstrating the remarkablyincreased healing rate of wounds treated with cream embodiments of thedisclosed wound-healing formulation.

Example 1

Patient presented with a post-operative left plantar heel woundfollowing a deep surgical excision to remove an invasive carcinoma.Artificial skin grafts were applied, but were unsuccessful. Topicalapplication of conventional silver-sulfadiazine-based and other woundcare creams also failed completely. Such unsuccessful conventionalproducts included Silvadene, Santyl, Medi-Honey, Betadine, and Dakin'sSolution. A cream embodiment of the disclosed wound-healing formulationwas prepared comprising the following ingredients: silver sulfadiazine1%, urogastrone 0.001%, water, stearyl alcohol, petrolatum, polyoxyl 40stearate, propylene glycol, isopropyl myristate, sorbitan monooleatewith 0.3% methylparaben, camphor 5%, menthol 10% and eucalyptus 4%. Thetemperature was adjusted between 65-75 degrees F. (+/−) 5 degrees F.,and was prepared by stirring continuously for 5 to 10 minutes. Theresulting mixture was thoroughly kneaded into a smooth cream whichappeared uniform in composition. The cream was applied every 48 hours topatient's left plantar heel wound. Wound was cleansed with normal salinesolution, followed by topical application of cream directly onto thewound and covered by a dry, sterile dressing. The wound healedcompletely in approximately 6 weeks. Patient was monitored throughoutthe study for any adverse reaction or experience. None were reported.

Example 2

Patient was a 38-year old diabetic male with a rare skin disorder. Therare skin disorder consisted of 1″ thick callus/hypertrophic skin whichcovered the entire plantar aspect of bilateral feet, extending from themetatarsal heads to both heels. Many different physicians had previouslyattempted treatment with multiple conventional topical wound care agentsincluding Santyl, Accuzyme, Panafil, Betadine, Dakin's Solution, Eucerincream, silver sulfadiazine-based formulations, menthol topical solutions(by themselves), and anti-bacterial topical creams. After several monthsof no improvement with such conventional wound care agents, patientunderwent surgery followed by topical wound care. The callus tissue wasresected in the operating room. This created various ulcerations notedon the entire plantar aspect of each foot (respectively, Wagner stage 2to stage 3 ulcerations). Patient was given different creams fortreatment, including Medihoney, Emuaid, polysporin, Santyl, Silvadene,Betadine, Collagen dressings, and Mepitel films. All of these wereunsuccessful after several months of use. Then, a cream embodiment ofthe disclosed wound-healing formulation was prepared comprising thefollowing ingredients: silver sulfadiazine 1%, urogastrone 0.001%,water, stearyl alcohol, petrolatum, polyoxyl 40 stearate, propyleneglycol, isopropyl myristate, sorbitan monooleate with 0.3%methylparaben, camphor 5%, menthol 10% and eucalyptus 4%. Thispreparation was then applied to the left plantar wound. The wound healedcompletely, and so the same treatment was applied to the right plantarwound. Both wounds healed successfully within four weeks. Patient hasbeen seen for approximately one year post-operatively with no recurrenceof wounds, and no further breakdown has been noted.

Example 3

Patient was a 57-year old non-insulin dependent diabetic female withvenous insufficiency of bilateral legs and feet. Her medical historyincluded hypertension, NIDDM, high cholesterol, diabetic neuropathy, anddepression. Patient also had a history of a stroke. The patient had 3wounds located on the left distal third of the anterior leg. Wounds wereapproximately 1-2 cm apart from one another. The most proximal woundmeasured 2 cm×2 cm×1 cm; the wound was fibro-granular in nature withsignificant serous drainage noted from the wounds. The second, middlewound was 1.5 cm×1.5 cm×1 cm, and was also fibro-granular in nature. Thethird, most distal wound was 2 cm×1 cm×0.5 cm and fibro-granular innature. Wounds were approximately 50% fibrotic and 50% granular. Patienthad been previously treated unsuccessfully with multiple topical agentsincluding conventional silver-sulfadiazine formulations. Such priortreatments included weekly debridements, topical debriding agents,absorbing agents, and oral antibiotics as well as multi-vitamins.Patient was seen twice a week for four weeks. Initially, the wounds weresharply debrided and all fibrotic tissue was removed. Then, a creamembodiment of the disclosed wound-healing formulation was preparedcomprising the following ingredients: silver sulfadiazine 1%,urogastrone 0.001%, water, stearyl alcohol, petrolatum, polyoxyl 40stearate, propylene glycol, isopropyl myristate, sorbitan monooleatewith 0.3% methylparaben, camphor 5%, menthol 10% and eucalyptus 4%. Thiscream was applied to a healthy, granular wound base twice a week forfour weeks. Wound was dressed with 4×4s, kling, and a kerlix dressing.The cream was uniformly applied throughout the entire aspect of allthree wound beds. A significant decrease in wound size and change incomposition of wound bed was evident in weeks 1 and 2. There was almostcomplete resolution by week 3. The wounds had completely resolved andhealed after 4 weeks. The skin was adequately covering what hadpreviously been exposed wound beds. Dressings were no longer needed atthis time and the patient is now seen for a routine follow up every 3-6months. Patient has been stable with no recurrence of wounds.

Example 4

Patient was a 49-year old insulin dependent diabetic male withhypertension and hypothyroidism and significant past medical history.Patient underwent left foot cheilectomy. The wound began dehiscing 7days post-operatively. Sutures loosened and a 2 inch linear incisionsite wound occurred. The wound was noted to 2 cm×0.25 cm×0.1 cm indimension. It was fibro-granular in nature and approximately 80% wasfibrotic and 20% granular with serous drainage noted. Patient was givenpost-operative antibiotic throughout the post-operative care time frame.Many conventional wound care topical products were initially used inattempts to heal surgical wound, including silver sulfadiazine-basedformulations, Santyl, collagen dressings, hydrocolloid dressings, andalginates. After 4 weeks, there was no improvement in wound healing withsharp debridement and topical wound care products. Accordingly, a creamembodiment of the disclosed wound-healing formulation was preparedcomprising the following ingredients: silver sulfadiazine 1%,urogastrone 0.001%, water, stearyl alcohol, petrolatum, polyoxyl 40stearate, propylene glycol, isopropyl myristate, sorbitan monooleatewith 0.3% methylparaben, camphor 5%, menthol 10% and eucalyptus 4%. Thispreparation was then applied every 3 days to the wound bed and coveredwith 4×4s, kling and kerlix dressings. Wound measurements were takenevery 3 days at every dressing change and improvement was noted in bothdimension and appearance of wound bed. After 4 weeks of continuoustreatment after every 3 days, the wound was completely closed with nodehiscence remaining. The patient had no recurrence of the wound.

Example 5

Patient was a 33-year old male with a non-healing left hallux wound.Patient had no significant past medical history, no known drug allergiesand prior surgeries consistent with tonsillectomy, hemorrhoid resection,and hernia repair. Patient had left hallux nail removed. Left halluxdorsal wound remained post-procedurally. The wound measured 1.5 cm×1.5cm×0.1 cm. The wound had slight serous drainage noted. Initial woundtreatment comprised of 4 weeks of application of betadine and topicalbacitracin ointment with no improvement. Following this treatment,camphor cream was applied by itself twice daily to left hallux woundsite. Minimal improvement was noted after 30 days of treatment. Upon day30, the wound measurement was noted to be 1.5 cm×1.25 cm×0.2 cm on thedorsal aspect of the left hallux. Mild serous drainage was noted, as wasnoted initially. At this time, camphor topical cream treatment wasdiscontinued and topical menthol-eucalyptus cream mixture was applied toleft hallux dorsal wound, twice daily for 30 days. Serial, weeklydebridements of the left hallux wound bed were performed with a #15surgical blade and a sharp curette. After 30 days of treatment, woundmeasurements were taken and the wound size was measured to beapproximately 1.25 cm×1.25 cm×0.1 cm. Very mild improvement was noted.Menthol-eucalyptus cream treatment was halted. A cream embodiment of thedisclosed wound-healing formulation was prepared comprising thefollowing ingredients: silver sulfadiazine 1%, urogastrone 0.001%,water, stearyl alcohol, petrolatum, polyoxyl 40 stearate, propyleneglycol, isopropyl myristate, sorbitan monooleate with 0.3%methylparaben, camphor 5%, menthol 10% and eucalyptus 4%. Thispreparation was then applied to the wound bed. As noted, upon initialapplication, the left dorsal hallux wound measured 1.25 cm×1.25 cm×0.1cm. Slight serous drainage was also noted. The wound was noted to befibrogranular in nature. The disclosed wound-healing formulation wasapplied once daily to the left hallux. Debridement of the woundcontinued to occur once a week and serial measurements were taken. Afterone week's treatment with the disclosed wound-healing formulation, thewound was measured to be 1 cm×1 cm×0.1 cm. Treatment continued with asimilar regimen in week 2. After 14 days, wound measurements were againtaken. The wound was measured to be 0.9 cm×0.7 cm×0.1 cm. Mild serousdrainage was again noted. With improvement noted, it was decided thatthe same regimen would continue. Treatment continued with a similarregimen in week 3. At the end of the 3^(rd) week, measurements wereagain taken. The wound was measured and noted to be 0.5 cm×0.5 cm×0.1 cmin depth. The regimen was continued for week 4, during which the woundwas again debrided and the disclosed wound-healing formulation wasapplied daily. At day 32, the wound had completely resolved. The woundhas not returned after 1 year of follow up and no further treatment.

Example 6

Patient was a 78-year old female with a past medical history of NIDDMand atrial fibrillation. Her past surgical history was significant formultiple foot surgeries including amputations of two digits on the leftfoot and amputation of a digit on the right foot. Also significant forpast surgical history was cataract surgery, OU, gallbladder surgery, andcarpal tunnel release to bilateral hands. Patient presented with aplantar hallux, non-healing wound, which measured 1 cm×1 cm×0.5 cm indepth. The wound was noted to have serosanguinous drainage for severalmonths. During this time, the wound was cleansed daily with saline and aconventional silver-sulfadiazine urogastrone cream (Hebermin) wasapplied as a first line of treatment. The wound was debrided once a weekwith a #15 surgical blade and a curette to remove all fibrotic,nonviable tissue from the wound bed. The wound bed was then dressed withbetadine, adaptic, 4×4s, and a light kling dressing. Hebermin was usedconsistently for 3 months. Weekly measurements of the wound were taken.Wound measurements went from 1 cm×1 cm×0.5 cm initially, to 0.8 cm×0.7cm×0.5 cm after three months of Hebermin treatment. Patient's woundshowed minimal improvement during the initial 3-month Hebermintreatment, during which time patent also faced multiple episodes ofcellulitis (which was treated with multiple antibiotics, includingClindamycin, Zithromax, and Bactrim DS). Hebermin cream alone was notadequate for wound healing. Patient's wound was then treated for 3months with a combination of camphor-eucalyptus-menthol cream, which wasagain applied daily to the wound on the left plantar hallux. Woundmeasurements started at 0.8 cm×0.7 cm×0.5 cm. Mild serous drainage wasnoted. Weekly debridements continued and weekly measurements were taken.Wound measurements decreased to 0.7 cm×0.6 cm×0.4 cm after 3 months ofcamphor-eucalyptus-menthol cream treatment. Stagnation of wound healingsolidified reasoning for a need for new treatment. At month 6, treatmentwas changed to the disclosed wound-healing formulation. A creamembodiment of the disclosed wound-healing formulation was preparedcomprising the following ingredients: silver sulfadiazine 1%,urogastrone 0.001%, water, stearyl alcohol, petrolatum, polyoxyl 40stearate, propylene glycol, isopropyl myristate, sorbitan monooleatewith 0.3% methylparaben, camphor 5%, menthol 10% and eucalyptus 4%. Thispreparation was applied once daily to the plantar left hallux. As noted,initial wound measurements were 0.7 cm×0.6 cm×0.4 cm. ABI testing wasperformed and adequate perfusion was noted. After daily applications ofthe disclosed wound-healing formulation and weekly debridements with theuse of a #15 surgical blade and curette as previously performed, thewound dimensions decreased significantly. After 3 weeks of continueduse, the wound completely resolved. No drainage, nor infectionpersisted. After 9 months post-wound healing of the left hallux plantarwound, the patient continued to be wound free and ambulate with nodifficulty.

The disclosed wound-healing formulation has been described above withreference to specific examples and actual cases in which embodimentsthereof were administered to promote healing of skin wounds such, asfor, example, arterial wounds, venous wounds, post-operative and othersurgical wounds, burns, dehisced wounds and ulcerations. It will beappreciated that the disclosed wound-healing formulation is not limitedto these exemplary cases and these applications.

Although the inventive material in this disclosure has been described indetail along with some of its technical advantages, it will beunderstood that various changes, substitutions and alternations may bemade to the detailed embodiments without departing from the broaderspirit and scope of such inventive material as set forth in thefollowing claims.

I claim:
 1. A topical formulation, comprising: (a) at least about 1%silver sulfadiazine; (b) at least about 0.001% urogastrone; and (c) atleast one ingredient selected from the group consisting of: (1) camphorin a clinically effective concentration for the topical formulation toincrease rate of wound healing over placebo; (2) menthol in a clinicallyeffective concentration for the topical formulation to increase rate ofwound healing over placebo; and (3) eucalyptus in a clinically effectiveconcentration for the topical formulation to increase rate of woundhealing over placebo.
 2. A topical formulation, comprising: (a) at leastabout 1% silver sulfadiazine; (b) at least about 0.001% urogastrone; and(c) at least two ingredients selected from the group consisting of: (1)camphor in a clinically effective concentration for the topicalformulation to increase rate of wound healing over placebo; (2) mentholin a clinically effective concentration for the topical formulation toincrease rate of wound healing over placebo; and (3) eucalyptus in aclinically effective concentration for the topical formulation toincrease rate of wound healing over placebo.
 3. A topical formulation,comprising: (a) at least about 1% silver sulfadiazine; (b) at leastabout 0.001% urogastrone; (c) camphor in a clinically effectiveconcentration for the topical formulation to increase rate of woundhealing over placebo; (d) menthol in a clinically effectiveconcentration for the topical formulation to increase rate of woundhealing over placebo; and (e) eucalyptus in a clinically effectiveconcentration for the topical formulation to increase rate of woundhealing over placebo.